Comparison of DNA damage and mutl, homolog1, mutshomolog2 expression status among subtypes in breast carcinoma cases

Breast cancer is the most common malignant tumor in women worldwide. It accounts for 30% of female cancer cases and is responsible for 15% of cancer-related deaths. Only a small subset (5-10%) of breast cancers are genetic. Among the best-known genetic mutations associated with breast cancer are mutations in the BRCA1 and BRCA2 genes. The BRCA1 gene is responsible for genome stability and affects DNA repair or recombination processes. Together with the BRCA2 gene product, the BRCA1 protein plays a role in repairing double-strand DNA breaks through homologous recombination. The DNA mismatch repair (MMR) mechanism is the primary system that corrects erroneous nucleotides inserted during DNA replication. The MMR mechanism prevents permanent damage by re-synthesizing the faulty region during post-replication, thereby repairing mismatched regions. Approximately 20% of sporadic cancer types arise from errors in the MMR pathway. In this study, cases diagnosed with invasive breast cancer at the Department of Medical Pathology of Ankara Bilkent City Hospital between February 2019 and June 2024, as well as cases among these that underwent BRCA gene analysis following diagnosis, were included. Hematoxylin and eosin (H&E)-stained slides and routine immunohistochemical slides for ER, PR, c-erbB2, and Ki67 of 79 cases classified by molecular subtypes were retrospectively re-evaluated. Tumor-infiltrating lymphocytes were assessed in H&E sections. Additionally, MLH1 and MSH2 antibodies were applied immunohistochemically on sections obtained from prepared paraffin blocks. In our study, a significant association was observed between the MLH1 and MSH2 staining percentage and tumor size, grade, and presence of metastasis across all subtypes. A significant relationship was also found between MLH1 and MSH2 staining intensity. The MSH2 staining intensity varied among subtypes, with the highest staining intensity observed in the triple-negative breast cancer subtype. The staining percentage and intensity of the cases were evaluated to obtain a final staining score (NBS-FSS), which was then compared. The MLH1 FSS score was found to be higher than the MSH2 FSS score across all subtypes. Our study aims to assess MLH1 and MSH2, markers for loss and preservation in familial cancer cases in other systems, in breast cancer cases with familial predisposition, and to explore the potential impact of their expression status on prognosis.